A research program is in progress dealing with several aspects of the metabolism and transport of vitamin A and of vitamin D. This program seeks to acquire detailed and fundamental information about the metabolism of these fat-soluble vitamins, and to apply this information where possible to the study of human biology and disease. Four major projects are in progress. Project One, on vitamin A transport and retinol-binding protein (RBP) metabolism, aims to examine the plasma vitamin A transport system in detail, with the goal of defining the cellular and molecular mechanisms involved in the regulation of RBP production and secretion by the liver. Studies with differentiated rat hepatoma cells in culture in vitro have indicated that these cell lines represent good models with which to explore these mechanisms. A study of immunoreactive RBP in liver microsomes is in progress. Project Two aims to characterize the enzymatic hydrolysis of retinyl esters in rat liver and to explore the metabolic regulation of retinyl ester hydrolase activity in liver. Information has been obtained about the enzymatic characteristics, subcellular localization, and chromatographic properties of retinyl palmitate hydrolase activity in liver homogenates from normal rats. Project Three aims to examine in detail the soluble intracellular binding proteins for retinol and for retinoic acid. Recent studies have resulted in the isolation and partial characterization of a soluble protein with binding specificity for retinoic acid from rat testis homogenates. Project Four focuses on the protein, called DBP, responsible for the transport of vitamin D and its metabolites in human plasma. The goals of this project are to characterize the chemical structure of this transport protein, to explore its interaction with various vitamin-D related sterols, and to study the effects of clinical disorders on the plasma levels and the metabolism of the protein.